(A) Field of the Invention
The present invention relates to a method for inspecting a grating biochip, and more particularly, to a method for inspecting a grating biochip using an optical inspection instrument.
(B) Description of the Related Art
The development of the biological technology field has directly affected the quality of human life, and has become a significant field of current scientific research. The development of the biochip has attracted significant attention due to its wide applications including medical inspection fields such as gene-analyzing and gene-sequencing research, the inspection for disease medications and the inspection of the properties of Chinese herbal medicine.
The conventional biochip inspection using the fluorescence technique has good detection sensitivity, but requires a complicated fluorescence labeling experiment to be performed in advance, and the fluorescence itself has unexpected risk of contaminating the sample under inspection. These factors affect the reliability of the experiment. A label-free inspection method has been proposed for solving these problems. Recently, label-free inspection methods have been proposed in succession, wherein the surface plasma resonance (SPR) attracts much attention due to its good detection sensitivity, but the inspection cost is relatively high since it requires the surface of the prism to be coated with a metal film. The prism coupled SPR is shown in FIG. 1, the surface between a sample 101 and a prism 103 must be coated with a metal film 102, and requires a TM-mode light source 105. Therefore, the cost is relatively high, only one single sample can be measured at a time, and the requirements of arranging the biochips in an array and inspecting multiple samples at a time cannot be satisfied.
Using an angular scatterometer to inspect a biochip is an innovative technique. The angular scatterometer has a good repeatability and reproducibility, and possesses many advantages such as optical non-destructiveness, quickness of use, and mass measurement. The surface plasma resonance is a method having the higher sensitivity for label-free biochip inspection, and it can be seen from the preliminary simulation result that the angular scatterometer and the surface plasma resonance have the same level of detection sensitivity. Thus, the angular scatterometer in fact has the potential to be developed as a quick and mass biochip inspection method having high sensitivity.
Recently, label-free inspection draws more and more attention in the biological sample inspection fields outside the conventional fluorescence method, since the complicated labeling process can be omitted and the problem of sample contamination no longer exists. Surface plasma resonance has the longer development history and is the method with the higher detection sensitivity of the current label-free measurement methods, which can be classified into a prism coupled SPR and a grating coupled SPR according to different excitation methods for the surface plasma resonance. The detail of the prism coupled SPR can refer to the disclosure of Raether H. (see: Surface plasma oscillations and their applications. In: Hass G, Francombe M, Hoffman R, eds. Physics of thin films. New York, N.Y.: Academic Press, 1977 vol. 9, p 145-261), while the detail of the grating coupled SPR can refer to the disclosure of Jennifer M. Brockman and Salvador M. Fernadez (see: Grating-coupled surface plasma resonance for rapid, label-free, array-based sensing, American Laboratory, June 2001, p 37-40).